Anticarcinogenic Potential of

A large number of laboratory studies have documented the chemo-preventive effect of tea, particularly green tea, against structurally diverse classes of chemical carcinogens as well as radiation-induced tumours (Table 8.1). Tea can suppress the carcinogenic response in many tissues. Moreover,

the anticarcinogenic effect of green tea is manifested at very low concentrations; when the model carcinogen was ^-methyl-^-nitrosourea, green tea extracts at the low concentration of 0.002% (w/v) effectively decreased colon carcinogenesis induced by the nitrosamine (Narisawa and Fukaura, 1993). The strength of brews consumed by humans is about 2-3%.

It appears that tea exerts its anticarcinogenic effect by modulating all stages of chemical carcinogenesis. In chemical systems, aqueous extracts of green and black tea prevented the formation of heterocyclic amines and the nitrosation of methylurea (Weisburger et al., 1994; Constable et al., 1996). Numerous studies have demonstrated the ability of tea aqueous extracts to impair the initiation stage of carcinogenesis, as exemplified by the marked suppression of the mutagenicity of chemical carcinogens, both direct- and indirect-acting, in in vitro studies (Bu-Abbas et al., 1994; Apostolides et al., 1996; Stavric et al., 1996; Yen and Chen, 1996). Furthermore, in in vivo human studies, the excretion of mutagens in the urine of women consuming cooked beef was suppressed by the intake of Tochu tea (Eucommia ulmoides) (Sasaki et al., 1996), a type of tea taken in Japan. Green tea, administered orally or topically, reduced the epidermis DNA binding of the two polycyclic aromatic hydrocarbons 3-methylcholanthrene and 7,12-dimethylbenz[a]anthracene (Wang et al., 1989). The in vivo binding of 2-amino-3-imidazo[4,5-/|quinoline (IQ) to hepatic DNA in rats was inhibited by infusions of green and black tea (Xu et al., 1996).

The anticarcinogenic effect of tea, however, is not exclusively due to inhibition of the initiation stage of carcinogenesis. Extracts of green and black decaffeinated tea inhibited DNA synthesis and cell proliferation in a rat hepatoma and a murine erythroleukaemia cell line (Lea et al., 1993). In the mouse skin model, aqueous extracts of green tea inhibited the promotion stage of carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene and promoted by 12-0-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice (Katiyar et al., 1993a). Similarly, aqueous extracts of green tea, administered to mice at the post-initiation stage, afforded protection against forestomach and lung tumours induced by benzo[a]pyrene and diethylnitrosamine in A/J mice (Katiyar et al., 1993b). The same workers demonstrated that green tea can also influence the progression stage of carcinogenesis, as exemplified by the ability of a tea polyphenolic fraction to inhibit the transformation of benign skin papillomas to squamous cell carcinomas induced by benzoyl peroxide and 4-nitroquinoline-AAoxide in SENCAR mice (Katiyar et al., 1993c, 1997). Clearly, green tea has the potential to suppress all the stages of chemical carcinogenesis.

Despite the numerous epidemiological studies which have examined the chemopreventive effects of tea, no convincing and consistent relationship between cancer incidence and tea consumption could be established (IARC, 1991; Kohlmeier et al., 1997; Yang et al., 1997; Ahmad et al., 1998). However, in most of these studies no adjustment was made for confounding factors such as consumption of fruit and vegetables. Moreover, no attempt was made to adjust for the method of preparation of the tea (e.g. the strength of the infusion, temperature of the water, the addition of milk, lemon, etc.). Such factors are likely to affect the composition of the tea brew. For example, it has been reported that the flavonoid content of tea prepared using tea bags is higher than that prepared using loose leaves (Hertog et al., 1993). It is noteworthy that in a recent population-based case-control study conducted in Shanghai, after adjusting for smoking, consumption of fruit and vegetables, and other factors, green tea consumption was inversely correlated with pancreatic and colorectal tumours (Ji et al., 1997).

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